Bruceine-D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction

Brucea javanica oil emulsion significantly improved the effect of anti-programmed cell death protein-1 immunotherapy.

Here, we collected 154 plant species in China ancient forests looking for novel efficient bioactive compounds for cancer treatments. We found 600 bioactive phyto-chemicals that kill liver cancer cells in vitro. First, we screen the plant extract's in vitro cytotoxicity inhibition of cancer cell growth using in vitro HepG2 cell lines and MTT cytotoxicity. The results from these initial MTT in vitro cytotoxicity tests show that the most efficient plants towards hepatoma cytoxicity is Cephaloaxis Sinensis, Mint bush (Elsholtzia Stauntoni) and Winged spindle tree (Euonymus Alatus). We then used in cell-counting kit-8 (CCK-8) to further understand in vivo tumor growth using nude mice and GC-MS and LC-QTOF-MS to analyze the composition of compounds in the extracts. Extracted chemically active molecules analyzed by network pharmacology showed inhibition on the growth of liver cancer cells by acting on multiple gene targets, which is different from the currently used orthodox drugs acting on only one target of liver cancer cells. Extracts from Cephaloaxis sinensis, Mint bush (Elsholtzia stauntoni) and Winged spindle tree (Euonymus alatus) induce apoptosis in hepatoma cancer cell line HepG2 with a killing rate of more than 83% and a tumor size decrease by 62–67% and a killing rate of only 6% of normal hepatocyte LO2. This study highlight efficient candidate species for cancer treatment providing a basis for future development of novel forest-based drugs to help meeting several of the UN SDGs and planetary health. 

Ancient forest plants possess cytotoxic properties causing liver cancer HepG2 cell apoptosis.

Anti-melanoma action of small molecular peptides derived from Brucea javanica(L.)Merr. globulin in vitro

Brusatol is a natural quassinoid terpenoid that shows a potential therapeutic use in treating various ailments. Recently, brusatol was shown to have anti-tumor activity and ameliorating chemoresistance or enhancing chemotherapeutic drug efficacy in vitro and in vivo cancer models, but its molecular mechanisms remained to be clarified. Here, we aim to investigate the roles of brusatol in oral squamous cell carcinoma (OSCC) cells and its possible mechanism, especially on tumor cell glycolytic metabolism. In this study, we found that brusatol exerted significant anti-tumor effects in OSCC cells by repressing tumor cells proliferation, cycles, migration, invasion, and colony formation and inducing cell apoptosis in vitro through MTT, cell cycle, cell migration and invasion, colony formation and cell apoptosis assays. The result of metabolic assay and Seahorse XF glycolysis stress test assay showed that brusatol directly targeted glycolysis by inhibiting the extracellular acidification rate represented by a decreased glycolysis, glycolytic capacity and reserve capacity, and repressing activity of the key glycolytic enzymes pyruvate kinase and hexokinase. We also found that the expression of glucose transporter 1 (GLUT1) and several important glycolysis related genes, including HIF-1α and c-Myc was downregulated by brusatol through real-time PCR. Furthermore, in vivo studies supported anti-tumor role for brusatol, demonstrating that brusatol inhibited tumor growth, angiogenesis, glycolysis metabolism and induction of apoptosis in OSCC cells nude mice xenografts. Our data clearly demonstrated the anti-tumor effects of brusatol in OSCC cells by targeting glycolytic metabolism, and it could become a promising tumor chemotherapeutic agent in oral cancer. 

Targeting tumor glycolysis metabolism in oral squamous cell carcinoma cells by brusatol

Efficacy and safety of Brucea javanica oil emulsion for liver cancer: A protocol for systematic review and meta-analysis.

The efficacy and safety of oral medications, onabotulinumtoxina (three doses) and transcutaneous tibial nerve stimulation (ttns) as non or minimally invasive treatment for the management of neurogenic detrusor overactivity (ndo) in adults: a systematic review and network meta-analysis

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Efficacy and safety of Brucea javanica oil emulsion for liver cancer: A protocol for systematic review and meta-analysis.

The efficacy and safety of oral medications, onabotulinumtoxina (three doses) and transcutaneous tibial nerve stimulation (ttns) as non or minimally invasive treatment for the management of neurogenic detrusor overactivity (ndo) in adults: a systematic review and network meta-analysis